The present invention relates to novel bis-dioxopiperazine derivatives, process for their preparation, antitumor agents comprising them and compositions containing them.
Bis-dioxopiperazine derivatives of the present invention are compounds represented by the following general formula (I): ##STR5## wherein R.sub.1 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms; R.sub.2 represents a hydrogen atom or a group of ##STR6## R.sub.3 and R.sub.4, which are respectively independent and are the same or different, represent respectively a lower alkyl group having 1 to 4 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms or a heterocyclic radical selected from the group consisting of substituted or unsubstituted piperidino, substituted or unsubstituted piperazino, substituted or unsubstituted morpholino and substituted or unsubstituted thiomorpholino, or R.sub.3 and R.sub.4 are bonded together to form a group of ##STR7## which represents a cyclic amino group selected from the group consisting of substituted or unsubstituted pyrrolidino, substituted or unsubstituted piperidino, substituted or unsubstituted piperazino, substituted or unsubstituted morpholino, substituted or unsubstituted thiomorpholino and substituted or unsubstituted thiadiazino; and the substituents of the heterocyclic radical and the cyclic amino group are selected from the group consisting of a lower alkyl group having 1 to 4 carbon atoms, oxo and phenyl, said cyclic amino group being not morpholino when R.sub.1 is a hydrogen atom and R.sub.2 is the group of ##STR8##
Several kinds of bis-dioxopiperazine derivatives have already been reported, especially 1,2-bis(4-morpholinomethyl-3,5-dioxopiperazin-1-yl)-ethane is known as an analogue of the compounds which the present invention concerns and its clinical efficacy as an antitumor and radio-potentiative agent was already evaluated (see Abstract, 8th International Congress of Pharmacology p441, 1981).
Based on the attractive biological activity of the known bis-dioxopiperazine derivatives, I, the inventor further carried out the synthetic study on these derivatives and found that the aforementioned bis-dioxopiperazine derivatives of the general formula (I) exhibit a broader spectrum of antitumor activity and anti-metastatic activity, thus accomplishing the present invention.